Our goal is to evaluate the clinical activity of recombinant immunotoxins in patients. HA22 is licensed to MedImmune who is sponsoring trials in B cell malignancies. A multi center phase 1 trial of HA22 (CAT-8015, moxetumomab pasudotox) in drug resistant hairy cell leukemia is completed and a MTD established. There have been no dose limiting toxicities and over 50% of patients have achieved a complete remission. We are working with MedImmune and CTEP to get FDA permission to carry out a pivotal trial in drug resistant hairy cell leukemia A multi center phase 1 trial of HA22 in refectory ALL is open. Clinical activity with 6 complete remissions has been observed. The original trial in which patients were treated with 6 doses every 21 days is complete. An additional cohort has been added in which patients are being treated with additional doses. This study is in collaboration with Dr. Alan Wayne of the Pediatric Oncology Branch. Trials with LMB2 in ATL are ongoing. R. Kreitman is the lead investigator in those trials.Dr. Hassan has completed the trial in mesothelioma in which newly diagnosed patients receive SS1P and standard chemotherapy and observed an unexpectedly high response rate. Based on the high number of CRs at the MTD a randomized phase 2 trial is being planned. Another SS1P trial is ongoing in which patients receive pentostatin plus cyclophosphamide with SS1P to try and prevent neutralizing antibody formation allowing more doses to be given. Six patients have been treated and the results are encouraging. Roche has taken a license from NIH to develop and bring into clinical trials a new less immunogenic variant of SS1P described below.A significant advance is described publication in J Clinical Oncolgy (FILL IN) showing a very high complete and partial response rate in patients with chemo-refractory Hairy Cell leukemia. These results have caused Medimmune and CTEP to plan a pivotal trial to gain FDA approval to use Moxe in this patient population.